A Study on the Efficacy of Androgen Deprivation Therapy Combined With Anti-PD-1 Therapy in Advanced Lung Cancer

A Clinical Investigation on the Efficacy of Leuprorelin Acetate (Androgen Deprivation Therapy) Combined With Sintilimab (Anti-PD-1) in Advanced Lung Cancer

Androgen Deprivation Therapy (ADT) triggers thymic revitalization and increases thymic output, enhancing baseline anti-tumor immunity and responses to immunotherapies. Anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. This study is to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

Study Overview

• Status: Recruiting
• Conditions: NSCLC, Stage III; NSCLC, Stage IV
• Intervention / Treatment: Drug: Sintilimab; Drug: Leuprorelin acetate + Sintilimab

Detailed Description

Immune checkpoint blockades (ICBs) are widely used in the clinical treatment of lung cancer. Studies have shown that the quantity and function of tumor-infiltrating lymphocytes (TILs) are associated with the effectiveness of PD-1 inhibitors in treating advanced NSCLC. The thymus is crucial for the differentiation, development, and maturation of T cells. With age, thymic atrophy leads to immunosenescence, significantly affecting baseline anti-tumor immunity and responses to immunotherapies. Preliminary findings have indicated that androgen deprivation therapy (ADT) not only directly induces apoptosis in prostate cancer cells but also may exert anti-tumor effects by promoting thymic regeneration. Furthermore, anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. Therefore, this study aims to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wangzhi Wei; Phone Number: (86)13941620158; Email: weiwangzhi@jzmu.edu.cn
• Study Contact Backup: Name: Shuangning Yang; Phone Number: (86)15138955506

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The Third Oncology Ward, First Affiliated Hospital of Zhengzhou University
      • Contact: Shuangning Yang; Phone Number: (86)15138955506
      • Principal Investigator: Liping Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

3.Inclusion Criteria:

1. Male patients aged ≥60 years.
2. ECOG performance status score of 0 ~1.
3. Expected survival time of more than 3 months.
4. Histologically or cytologically diagnosed advanced lung cancer according to the TNM staging system established by AJCC.
5. Patients who have not previously received any anti-PD-1 treatment.
6. Patients with adequate bone marrow function, no significant hepatic, renal, or coagulation dysfunction as per laboratory test criteria.

7. At least one tumor lesion meeting the following criteria:

   • No prior local treatments such as radiotherapy
   • Not biopsied during the screening period (if biopsy needed, baseline tumor assessment at least 14 days after the screening biopsy).
   • Measurable at baseline (longest diameter of the lesion ≥10 mm; For a lymph node, short diameter ≥15 mm).
   • If only one measurable lesion, no prior local treatments such as radiotherapy.
8. Ability to understand and voluntarily sign a written informed consent form.
9. Willingness to follow the study protocol and follow-up examinations.

Exclusion Criteria:

• Exclusion of cases that do not meet the inclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Treatment Group; 40 cases in this group to receive the standard conventional treatment (Chemotherapy + PD-1 Monoclonal Antibody)	Drug: Sintilimab; PD-1 inhibitor; Other Names: Anti-PD-1 monoclonal
Experimental: Conventional Treatment Combined with Leuprolide Group; 40 cases in this group to receive the standard conventional therapy (Chemotherapy + PD-1 Monoclonal Antibody) combined with Leuprorelin acetate, 3.75 mg	Drug: Leuprorelin acetate + Sintilimab; Leuprolide, an FDA-approved GnRH agonist, reduces sex hormone production and is widely used in clinical practice.; Other Names: Leuprolide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Complete Response (CR)	Disappearance of all target lesions, with nodular diseases excluded and target nodules reduced to <10mm in short axis.	Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Number of Participants with Partial Response (PR)	Reduction of at least 30% in the sum of diameters of all measurable target lesions compared to baseline	Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Number of Participants with Disease Progression (PD)	A 20% increase in the sum of the diameters of all measurable target lesions over the entire study period (using the smallest baseline value if it is the smallest), coupled with an absolute increase in the sum of diameters of at least 5mm. The appearance of one or more new lesions is also considered disease progression.	Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Number of Participants with Stable Disease (SD)	Lesion reduction not meeting PR criteria nor sufficient increase for PD, falling in between these two endpoints. The minimum sum of diameters during the study period can be used as a reference.	Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Quantity of Peripheral Blood Lymphocytes	Assessment of peripheral blood lymphocyte quantity, comparing patients before and after a treatment cycle	Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment
Composition of Peripheral Blood Lymphocytes	Assessment of peripheral blood lymphocyte composition, comparing patients before and after a treatment cycle	Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.
Status of Recent Thymic Emigrants (RTEs)	Assessment of the status of Recent Thymic Emigrants (RTEs), comparing patients before and after a treatment cycle	Evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.

Collaborators and Investigators

• Sponsor: Jinzhou Medical University
• Collaborators: The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Yu Zhang, Professor, Jinzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 6, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; PD-1 inhibitor; Androgen Deprivation Therapy （ADT）; Leuprorelin acetate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropin-Releasing Hormone; Leuprolide; sintilimab; spartalizumab
• Other Study ID Numbers: NSFC-32230037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We currently do not plan to share individual patient data (IPD) with other researchers due to confidentiality concerns and ethical restrictions. Additionally, the data collected in this study are considered proprietary and are crucial for ongoing and future research projects.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No